92897-32-0

Upstream product

• 2055-46-1 3,4,5,6-tetrahydropyrimidine-2-thione 
• 1703-23-7 N,N'-bis(chloroacetyl)piperazine 
• 42951-91-7 2-chloro-1-(4-methylpiperazin-1-yl)ethan-1-one hydrochloride 
• 93378-52-0 1-methyl-4-(2-tetrahydropyrimidinylthioacetyl)piperazine dihydrochloride 
• 79-11-8 chloroacetic acid 
• 2055-46-1 2-mercapto-3,4,5,6-tetrahydropyrimidine 
• 79-08-3 bromoacetic acid 
• 105-39-5 chloroacetic acid ethyl ester 

Downstream Products

• 92897-33-1 6,7-dihydro-2-benzylidene-5H-thiazolo<3,2-a>pyrimidine-3(2H)-one 
• 92897-47-7 2-[1-(4-Methoxy-phenyl)-meth-(Z)-ylidene]-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidin-3-one 

Relevant academic research and scientific papers

Heterocyclic substituted styrene compound and use thereof

The invention relates to a heterocyclic substituted styrene compound and its use. The invention discloses a heterocyclic radical, alkoxy and halogen modified styrene compound. Results of inhibition activity of the compound against Syk (spleen tyrosine kinase) show that the compound has inhibition activity against the Syk (spleen tyrosine kinase), and part of the compound has stronger inhibition activity against the Syk, and a structure foundation for further design and development of new Syk inhibitor-class rheumatoid arthritis (RA) therapy drugs is laid.

Discovery of Benzylidene Derivatives as Potent Syk Inhibitors: Synthesis, SAR Analysis, and Biological Evaluation

Four scaffolds of varied benzylidene derivatives were synthesized and evaluated as Syk inhibitors for the treatment of rheumatoid arthritis (RA). Among these 31 compounds, 3-benzylidene pyrrolidine-2,5-dione derivatives (including 12k) universally showed good Syk inhibitory activities in the low micromolar to submicromolar range. In the cellular profiling, compound 12k, the most efficient compound, showed excellent antiproliferative activity against fibroblast-like synoviocytes (FLS)-RA, and demonstrated potencies for suppression of IL-6 and MMP-3 secretion almost equal to R406 (positive control). The oral efficacy of 12k in the murine collagen-induced arthritis model was significant, despite being weaker than R406. Taken together, all preliminary pharmacological results supported 12k as a potential small-molecule inhibitor targeting Syk for the treatment of RA.

Discovery, synthesis and SAR analysis of novel selective small molecule S1P4-R agonists based on a (2Z,5Z)-5-((pyrrol-3-yl)methylene)-3- alkyl-2-(alkylimino)thiazolidin-4-one chemotype

High affinity and selective S1P4 receptor (S1P4-R) small molecule agonists may be important proof-of-principle tools used to clarify the receptor biological function and effects to assess the therapeutic potential of the S1P4-R in diverse disease areas including treatment of viral infections and thrombocytopenia. A high-throughput screening campaign of the Molecular Libraries-Small Molecule Repository was carried out by our laboratories and identified (2Z,5Z)-5-((1-(2-fluorophenyl)-2,5-dimethyl-1H- pyrrol-3-yl)methylene)-3-methyl-2-(methylimino) thiazolidin-4-one as a promising S1P4-R agonist hit distinct from literature S1P4-R modulators. Rational chemical modifications of the hit allowed the identification of a promising lead molecule with low nanomolar S1P4-R agonist activity and exquisite selectivity over the other S1P 1-3,5-Rs family members. The lead molecule herein disclosed constitutes a valuable pharmacological tool to explore the effects of the S1P4-R signaling cascade and elucidate the molecular basis of the receptor function.

REACTION OF CYCLIC THIOUREAS WITH CHLOROACYLPIPERAZINES

S-Alkylation products are formed in the reaction of tetrahydropyrimidine-2-thione and hexahydro-1,3-diazepine-2-thione with chloroacylpiperazines in dimethylformamide at room temperature; dihydrothiazolopyrimidine and tetrahydrothiazolo-diazepine systems are obtained in refluxing ethanol.It is shown that the S-alkyl derivatives are very readily converted to condensed systems.